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This genomic diversity gives rise to many competing clones that may drive the biological trajectory of the disease. Previous large-scale sequencing efforts have focused on the evolutionary process in metastatic prostate cancer, revealing a potential clonal progression to castration resistance. However, the clonal origin of synchronous lymph node (LN) metastases in primary disease is still unknown. Here, we perform multi-region, targeted next generation sequencing and construct phylogenetic trees in\u00a0men with prostate cancer with synchronous LN metastasis to better define the pathologic and molecular features of primary disease most likely to spread to the LNs. Collectively, we demonstrate that a combination of histopathologic and molecular factors, including tumor grade, presence of extra-prostatic extension, cellular morphology, and oncogenic genomic alterations are associated with synchronous LN metastasis.<\/jats:p>","DOI":"10.1038\/s41467-024-48629-y","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T14:02:16Z","timestamp":1716300136000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3928-9476","authenticated-orcid":false,"given":"Udit","family":"Singhal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9227-0168","authenticated-orcid":false,"given":"Srinivas","family":"Nallandhighal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7614-9931","authenticated-orcid":false,"given":"Jeffrey J.","family":"Tosoian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinh M.","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Stangl-Kremser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Jen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razeen","family":"Karim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komal R.","family":"Plouffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-0603","authenticated-orcid":false,"given":"Todd M.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Cieslik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Lucian\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrokh F.","family":"Shariat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Finocchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Dambrosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4969-5216","authenticated-orcid":false,"given":"Claudio","family":"Doglioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9282-3415","authenticated-orcid":false,"given":"Arul M.","family":"Chinnaiyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Tomlins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Briganti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9520-0480","authenticated-orcid":false,"given":"Ganesh S.","family":"Palapattu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8254-5404","authenticated-orcid":false,"given":"Aaron M.","family":"Udager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7461-7079","authenticated-orcid":false,"given":"Simpa S.","family":"Salami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"48629_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel, R. 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JJT is a co-founder with minor equity interest in LynxDx, which has licensed urinary biomarkers unrelated to this project. S.A.T has received travel support from and had a sponsored research agreement with Compendia Bioscience\/Life Technologies\/ThermoFisher. The University of Michigan and Brigham and Women\u2019s Hospital have been issued a patent on <i>ETS<\/i> gene fusions (US8969527B2 \u201cRecurrent gene fusions in prostate cancer\u201d) in prostate cancer on which S.A.T. and A.M.C. are co-inventors. The diagnostic field of use was licensed to Hologic\/Gen-Probe, Inc., which has sublicensed rights to Roche\/Ventana Medical Systems. S.A.T. has served as a consultant for and received honoraria from Janssen, AbbVie, Sanofi, Almac Diagnostics and Astellas\/Medivation. S.A.T. has sponsored research agreements with Astellas and GenomeDX. S.A.T. is a co-founder and Chief Medical Officer for Strata Oncology. T.M.M. has received research funding from MDxHealth, Myriad Genetics, and GenomeDx. T.M.M. has served as a consultant for Myriad Genetics. U.S. has received research funding from Merck & Co., Inc. S.S.S. is on a study advisory committee for Bayer Pharma and has a non-sponsored research agreement with GenomeDx. The other authors have declared that no conflict of interest exists.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4341"}}